title: Disc1 point mutations in mice affect development of the cerebral cortex.
abstract: Disrupted-in-Schizophrenia 1 (DISC1) is a strong candidate gene for schizophrenia and other mental disorders. DISC1 regulates neurodevelopmental processes including neurogenesis, neuronal migration, neurite outgrowth, and neurotransmitter signaling. Abnormal neuronal morphology and cortical architecture are seen in human postmortem brain from patients with schizophrenia. However, the etiology and development of these histological abnormalities remain unclear. We analyzed the histology of two Disc1 mutant mice with point mutations (Q31L and L100P) and found a relative reduction in neuron number, decreased neurogenesis, and altered neuron distribution compared to wild-type littermates. Frontal cortical neurons have shorter dendrites and decreased surface area and spine density. Overall, the histology of Disc1 mutant mouse cortex is reminiscent of the findings in schizophrenia. These results provide further evidence that Disc1 participates in cortical development, including neurogenesis and neuron migration.
authors.affiliation: Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8.
authors.forename: Frankie H F
authors.initials: FH
authors.lastname: Lee
authors.forename: Marc P
authors.initials: MP
authors.lastname: Fadel
authors.forename: Kate
authors.initials: K
authors.lastname: Preston-Maher
authors.forename: Sabine P
authors.initials: SP
authors.lastname: Cordes
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Clapcote
authors.forename: David J
authors.initials: DJ
authors.lastname: Price
authors.forename: John C
authors.initials: JC
authors.lastname: Roder
authors.forename: Albert H C
authors.initials: AH
authors.lastname: Wong
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000196:embryology* / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D006131:Growth Inhibitors / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011247:Pregnancy
chemical_list: C498794:Disc1 protein, mouse; D006131:Growth Inhibitors; D009419:Nerve Tissue Proteins